Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 707
Filtrar
1.
Int J Biol Macromol ; 201: 67-74, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995661

RESUMO

Lignin, especially Brauns native lignin (BNL), from Chinese quince (Chaenomeles sinensis) fruit represents a potential source of natural antioxidants. However, the highly inhomogeneous structure and the carbohydrate impurity reduce the antioxidant properties of BNL. Accordingly, a sequential aqueous acetone fractionation was used to prepare pure lignin fractions with homogeneous molecular structures; these fractions showed strong antioxidant properties. Analytical results showed that the yields of F50% and F60% exceeded 20% (i.e., 20.6% and 24.1%, respectively). The sugar impurities in BNL were mainly retained in the F30% and F40% fractions. For all fractions, molecular weight increased as the acetone concentration increased. The results from 2D HSQC NMR and 31P NMR indicated that the number of lignin linkages (ß-O-4', ß-ß' and ß-5') and functional groups (S-OH, G-OH, H-OH, and COOH) of these fractions varied with their molecular weights. Antioxidant assays showed that F40%, F50% and F60% had higher antioxidant properties than BNL. Overall, the study provides a simple, environmentally friendly fractionation method to prepare lignin with various structural features and strong antioxidant properties from Chinese quince fruit. These lignin fractions have promising application in some fields with high value, such as antioxidants production, biomaterials, packaging materials, and drug delivery and so on.

2.
J Hazard Mater ; 426: 128125, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34971988

RESUMO

Neonicotinoids have been banned in some countries because of increased nontarget resistance and ecological toxicity. Cycloxaprid is a potentially promising substitute, but its metabolism in plants is still poorly understood. The study aims to clarify the translocation of cycloxaprid, identify its metabolites, propose possible metabolic pathways and compare differences between enantiomers in oilseed rape via 14C tracing technology and HPLC-QTOF-MS. The results showed that most cycloxaprid remained in the treated leaves, and only a small amount translocated to the anthers. Seven metabolites were identified, and the possible metabolic pathway was divided into two phases. Phase Ⅰ metabolism included two metabolites obtained via cleavage of the oxa-bridged seven-membered ring. Phase II metabolism was responsible for glucose conjugate formation. The possible metabolic pathways revealed that the proportion of phase I metabolites gradually decreased over time, and the phase II metabolites transformed from monosaccharide and disaccharide conjugates to trisaccharide and tetrasaccharide conjugates. The levels of metabolites were significantly different between the enantiomers. In particular, the main metabolite was M4, which has confirmed biological toxicity. M2 was the only metabolite detected in rapeseed. The results will promote the scientific application of cycloxaprid in agriculture and could have implications for assessing environmental risk.

3.
Anatol J Cardiol ; 25(12): 872-879, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34866581

RESUMO

OBJECTIVE: The prognostic value of interleukin-6 (IL-6) in patients with atrial fibrillation (AF) has not been fully elucidated. Therefore, we conducted a cohort study and a meta-analysis to assess the predictive value of IL-6 for stroke and mortality in patients with AF. METHODS: A cohort study was performed in newly diagnosed non-valvular patients with AF. A total of 217 patients with AF were followed up for a mean of 27 months. A multivariate Cox regression analysis was used to evaluate the association between IL-6 and stroke/all-cause mortality. The incremental value was also assessed by adding IL-6 to the CHA2DS2-VASc score. Besides, a meta-analysis of all reported cohort studies and our cohort study was conducted to validate the association of circulating IL-6 and stroke/mortality in patients with AF. RESULTS: Our cohort study showed that elevated plasma level of IL-6 was an independent risk factor for predicting stroke [hazard ratio (HR)=3.81; 95% confidence interval (CI), 1.11-13.05; p=0.033] and all-cause mortality (HR=3.11; 95% CI, 1.25-7.72; p=0.015) in patients with AF. Adding IL-6 levels to CHA2DS2-VASc score showed limited improvement of the predictive power for stroke [area under curve (AUC) from 0.81 to 0.88, p=0.006]. Meta-analysis confirmed that increased circulating level of IL-6 was significantly associated with increased risk of stroke (pooled HR=1.97; 95% CI, 1.22-3.17; p=0.006) and all-cause mortality (pooled HR=2.73; 95% CI, 2.29-3.25; p<0.001). CONCLUSION: Increased circulating level of IL-6 was significantly associated with greater risk of stroke and all-cause mortality in patients with AF. Adding IL-6 biomarker to the CHA2DS2-VASc score may help to determine the management of AF treatment.

4.
Life (Basel) ; 11(12)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34947920

RESUMO

Group A rotaviruses (RVAs) are major enteric pathogens causing infections in calves. To investigate the epidemiological characteristics and genetic diversity of bovine rotavirus (BRV), 233 fecal samples were collected from calves with diarrhea in northeast China. The samples were analyzed for sequences encoding the inner capsid protein VP6 (subgroup) and the outer capsid proteins VP7 and VP4 (G and P type, respectively) using RT-PCR. Ten of the 233 samples (4.3%) were identified as BRV positive and were used for virus isolation and sequence analysis, revealing that all strains analyzed were of the G6P[1] genotype. The isolates exhibited high VP6 sequence identity to the USA cow RVA NCDV strain (>99% amino acid identity) and were further shown to be closely related to Japanese cow RVA BRV101 and Israelian human RVA G6P[1] strains, with >99% amino acid identity to VP7 and VP4 proteins, respectively. Comparative analyses of genome-predicted amino acid sequences between the isolates and the NCDV strains indicated that the antigenicity and infectivity of the strains isolated had changed. In this study, BRV genotypes and the genetic diversity among vaccinated cattle herds were monitored to provide epidemiological data and references for early diagnosis, allowing for early detection of new, potentially pathogenic RVA strains.

5.
Cell Discov ; 7(1): 121, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34930913

RESUMO

Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (Pcombined = 8.90 × 10-10). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.

6.
Sci Total Environ ; 813: 152545, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34952065

RESUMO

A series of vanillin derivatives have recently been synthesized as effective candidate antiviral agents, with vanisulfane exhibiting pronounced curative and protective activities against cucumber mosaic virus and potato virus Y. However, research on some new pesticides usually ignores their various metabolites and sex-related toxicity. Assisted by 14C labeling, a trial was conducted to investigate the tissue distribution, excretion, and metabolism of vanisulfane in male and female rats for the first time. The results showed that 83.30-87.51% of applied 14C activity was excreted in urine and feces within 24 h of oral administration, and 14C was most abundant in the liver and kidney in both sexes. Interestingly, sex differences were observed in the experiment, with lower body clearance in males than in females 24 h after treatment and preferences for biliary and renal excretion of the pesticide in male and female rats, respectively. A high degradation rate was found for vanisulfane in the plasma; thus, the metabolites of vanisulfane were investigated using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) combined with 14C labeling. One glucuronic acid conjugate and two oxidation metabolites were detected, supporting the monitoring of vanisulfane in vivo. Additionally, rats exposed to vanisulfane exhibited hepatic steatosis in both sexes, along with mild gonadal effects in males. This research offers an effective method for conducting environmental behavioral research and provides new insights for evaluating the potential risks of novel pesticides in mammals from a sex perspective.

7.
AMB Express ; 11(1): 157, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837552

RESUMO

Bacterial biofilms formation is one of the major reasons for treatment failure in chronic wound infections. Therefore, diagnostic biomarkers remain the best option for prevention and treatment of chronic wound infections by biofilms. Herein, Pseudomonas aeruginosa PAO1 was used to mimic biofilm development in porcine skin explants wells as ex vivo wound model. The microscopic imaging showed that PAO1 in porcine skin explants wells formed micro-colonies at 24 h, developed mushroom-like structure at 48 h, and at 72 h mushroom-like structure disappeared, remaining a thin bacterial lawn. RNA-seq data analysis revealed that the expression levels of genes involved in the type II hxc secretion system were significantly higher in biofilms than in planktonic cells, especially the expression of lapA encoding alkaline phosphatase. However, the expression levels of genes associated with denitrification pathway were markedly decreased in biofilms, especially the transcription of nirS encoding nitrite reductase to produce nitric oxide (NO). Therefore, their expressions and products were further detected using RT-qPCR and biochemical assays, respectively. The results found that the expression of lapA and alkaline phosphatase activity were induced, but the expression of nirS and intracellular NO were reduced at the whole biofilms cycle. The study indicates that LapA and NO would play an important role for P. aeruginosa biofilm formation in chronic wound infections. LapA would serve as potential target to monitor chronic wound infections by P. aeruginosa biofilms. Inducing NO would be used to treat chronic wound infections due to P. aeruginosa biofilms.

8.
J Neurol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839456

RESUMO

BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

9.
Mol Microbiol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797006

RESUMO

Numerous transcription factors (TFs) in ascomycete fungi play crucial roles in cellular processes; however, how most of them function is poorly understood. Here, we identified and characterized a novel TF, CxrC (POX01387), acting downstream of the key TF CxrA, which is essential for plant-biomass-degrading-enzyme (PBDE) production in Penicillium oxalicum. Deletion of cxrC in P. oxalicum significantly affected the production of PBDEs, as well as mycelial growth and conidiospore production. CxrA directly repressed the expression of cxrC after about 12 hr following switch to Avicel culture. CxrC bound the promoters of major PBDE genes and genes involved in conidiospore development. CxrC was found to bind the TSSGTYR core sequence (S: C and G; Y: T and C; R: G and A) of the important cellulase genes cbh1 and eg1. Both N- and C-terminal peptides of CxrC and the CxrC phosphorylation were found to mediate its homodimerization. The conserved motif LPSVRSLLTP (65-74) in CxrC was found to be required for regulating cellulase production. This study reveals novel mechanisms of TF-mediated regulation of the expression of PBDE genes and genes involved in cellular processes in an ascomycete fungus.

10.
Chemosphere ; : 132885, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34774905

RESUMO

The insecticide imidacloprid (IMI), which is used worldwide, pollutes environments and has significant ecotoxicological effects. Microbial metabolism and photolysis are the major pathways of IMI degradation in natural environments. Several studies have reported that the metabolites of IMI nitroreduction are more toxic to some insects and mammals than IMI itself. Thus, environmental degradation of IMI may enhance the ecotoxicity of IMI and have adverse effects on non-target organisms. Here, we report that an actinomycete-Gordonia alkanivorans CGMCC 21704-transforms IMI to a nitroreduction metabolite, nitroso IMI. Resting cells of G. alkanivorans at OD600 nm = 10 transformed 95.7% of 200 mg L-1 IMI to nitroso IMI in 4 d. Nitroso IMI was stable at pH 4-9. However, it rapidly degraded under sunlight via multiple oxidation, dehalogenation, and oxidative cleavage reactions to form 10 derivatives; the half-life of nitroso IMI in photolysis was 0.41 h, compared with 6.19 h for IMI. Acute toxicity studies showed that the half maximal effective concentration (EC50) values of IMI, nitroso IMI, and its photolytic metabolites toward the planktonic crustacean Daphnia magna for immobilization (exposed to the test compounds for 48 h) were 17.70, 9.38, 8.44 mg L-1, respectively. The half-life of nitroso IMI in various soils was also examined. The present study reveals that microbial nitroreduction accelerates IMI degradation and the nitroso IMI is easily decomposed by sunlight and in soil. However, nitroso IMI and its photolytic products have higher toxicity toward D. magna than the parent compound IMI, and therefore increase the ecotoxicity of IMI.

11.
Environ Sci Technol ; 55(23): 15680-15693, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34775752

RESUMO

Molecular analyses help to investigate the key precursors and chemical processes of secondary organic aerosol (SOA) formation. We obtained the sources and molecular compositions of organic aerosol in PM2.5 in winter in Beijing by online and offline mass spectrometer measurements. Photochemical and aqueous processing were both involved in producing SOA during the haze events. Aromatics, isoprene, long-chain alkanes or alkenes, and carbonyls such as glyoxal and methylglyoxal were all important precursors. The enhanced SOA formation during the severe haze event was predominantly contributed by aqueous processing that was promoted by elevated amounts of aerosol water for which multifunctional organic nitrates contributed the most followed by organic compounds having four oxygen atoms in their formulae. The latter included dicarboxylic acids and various oxidation products from isoprene and aromatics as well as products or oligomers from methylglyoxal aqueous uptake. Nitrated phenols, organosulfates, and methanesulfonic acid were also important SOA products but their contributions to the elevated SOA mass during the severe haze event were minor. Our results highlight the importance of reducing nitrogen oxides and nitrate for future SOA control. Additionally, the formation of highly oxygenated long-chain molecules with a low degree of unsaturation in polluted urban environments requires further research.

12.
Aging Cell ; : e13508, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751998

RESUMO

An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR-125a-5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR-125a-5p suppressed mitochondrial function and increased cellular DNA damage in GC2 cells. We also found that miR-125a-5p perturbed embryo development at specific morula/blastocyst stages. Mechanistically, we confirmed that miR-125a-5p disturbed the mitochondrial function by targeting Rbm38 and activating the p53 damage response pathway, and induced a developmental delay in a p21-dependent manner. Our study revealed an important role of miR-125a-5p in sperm function and early embryo development of aging males, and provided a fresh view to comprehend the aging process in sperm.

13.
Plant Physiol ; 187(4): 2469-2484, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34618061

RESUMO

The endoplasmic reticulum (ER) contains an elaborate protein quality control network that promotes protein folding and prevents accumulation of misfolded proteins. Evolutionarily conserved UBIQUITIN-ASSOCIATED DOMAIN-CONTAINING PROTEIN 2 (UBAC2) is involved in ER-associated protein degradation in metazoans. We have previously reported that two close UBAC2 homologs from Arabidopsis (Arabidopsis thaliana) not only participate in selective autophagy of ER components but also interact with plant-specific PATHOGEN-ASSOCIATED MOLECULAR PATTERN (PAMP)-INDUCED COILED COIL (PICC) protein to increase the accumulation of POWDERY MILDEW-RESISTANT 4 callose synthase. Here, we report that UBAC2s also interacted with COPPER (Cu) TRANSPORTER 1 (COPT1) and plasma membrane-targeted members of the Cu transporter family. The ubac2 mutants were significantly reduced in both the accumulation of COPT proteins and Cu content, and also displayed increased sensitivity to a Cu chelator. Therefore, UBAC2s positively regulate the accumulation of COPT transporters, thereby increasing Cu uptake by plant cells. Unlike with POWDERY MILDEW RESISTANCE 4, however, the positive role of UBAC2s in the accumulation of COPT1 is not dependent on PICC or the UBA domain of UBAC2s. When COPT1 was overexpressed under the CaMV 35S promoter, the increased accumulation of COPT1 was strongly UBAC2-dependent, particularly when a signal peptide was added to the N-terminus of COPT1. Further analysis using inhibitors of protein synthesis and degradation strongly suggested that UBAC2s stabilize newly synthesized COPT proteins against degradation by the proteasome system. These results indicate that plant UBAC2s are multifunctional proteins that regulate the degradation and accumulation of specific ER-synthesized proteins.

14.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34599099

RESUMO

Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates Gs while SV1 selectively couples to ß-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the apo state or GHRH-bound state in complex with the Gs protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gs versus ß-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward ß-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.

15.
J Ethnopharmacol ; : 114669, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600079

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sugemule-3 decoction (SD-3) is a commonly used prescription in Mongolian medicine which composed of the herbs Baidoukou (the fruit of Amomum compactum Sol. ex Maton), Baijusheng (the fruit of Lactuca sativa L.) and Biba (Piper longum L.). SD-3 has remarkable effect on the cardiovascular diseases, but its pharmacological mechanism has not been elucidated. AIM OF THIS STUDY: To evaluate the cardioprotective effects and the potential mechanisms of the ethanol extracts of SD-3 against isoproterenol (ISO)-induced heart failure (HF) in rats. MATERIAL AND METHODS: The ethanol extracts of SD-3 were prepared and analyzed by LC-ESI-MS/MS. One hundred male Wistar rats were randomly divided into five groups: control, ISO (HF) and different doses of SD-3 (0.4, 0.2, 0.1 g/kg/d) groups. HF model rats were established by intraperitoneal injecting of ISO. The left ventricular function was evaluated by echocardiography. Myocardial injury and fibrosis were examined by hematoxylin-eosin (HE) and Masson staining. Western-blot analysis was performed to determine the protein expression of apoptosis and mitochondrial dynamics in all the groups. Moreover, the structural changes in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy. RESULTS: Fifteen compounds were detected in the ethanol extracts of SD-3, include piperine, piperanine, etc. Rats administered with ISO showed a significant decline in the left ventricular function. The cardiac histopathological changes such as local necrosis, interstitial oedema, and cardiac fibrosis were also observed in the ISO group. The treatment with SD-3 significantly inhibited these effects of ISO. ISO was found to increase the protein expression of Bax, cleaved-PARP and cleaved-caspase-3, -7 -9, destroy the balance between mitochondrial fusion and fission, and alter the mitochondrial morphology. The ethanol extracts of SD-3 could rebalance mitochondrial fusion and fission, and ameliorates the morphological abnormalities induced by ISO in mitochondria. CONCLUSION: The current study demonstrated that ethanol extracts of SD-3 improved isoprenaline-induced cardiac hypertrophy and fibrosis through inhibiting cardiomyocyte apoptosis and regulating the mitochondrial dynamics.

17.
J Cell Sci ; 134(21)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34651179

RESUMO

Motile cilia have a '9+2' structure containing nine doublet microtubules and a central apparatus (CA) composed of two singlet microtubules with associated projections. The CA plays crucial roles in regulating ciliary motility. Defects in CA assembly or function usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of most CA projections remain largely unknown. Here, we combined genetic, proteomic and cryo-electron tomographic approaches to compare the CA of wild-type Chlamydomonas reinhardtii with those of three CA mutants. Our results show that two proteins, FAP42 and FAP246, are localized to the L-shaped C1b projection of the CA, where they interact with the candidate CA protein FAP413. FAP42 is a large protein that forms the peripheral 'beam' of the C1b projection, and the FAP246-FAP413 subcomplex serves as the 'bracket' between the beam (FAP42) and the C1b 'pillar' that attaches the projection to the C1 microtubule. The FAP246-FAP413-FAP42 complex is essential for stable assembly of the C1b, C1f and C2b projections, and loss of these proteins leads to ciliary motility defects.

18.
Front Cell Dev Biol ; 9: 673873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692669

RESUMO

Background: Gene expression and alternative splicing (AS) can promote cancer development via complex mechanisms. We aimed to identify and verify the hub AS events and splicing factors associated with the progression of colorectal cancer (CRC). Methods: RNA-Seq data, clinical data, and AS events of 590 CRC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG, and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in five CRCs. Results: In this study, we first compared differentially expressed genes and gene AS events between normal and tumor tissues. Differentially expressed genes were different from genes with differentially expressed AS events. Prognostic analysis and co-expression network analysis of gene expression and gene AS events were conducted to screen five hub gene AS events involved in CRC progression: EPB41L2, CELF2, TMEM130, VCL, and SORBS2. Using qRT-PCR, we also verified that the gene AS events SORBS2 were downregulated in tumor tissue, and gene AS events EPB41L2, CELF2, TMEM130, and VCL were upregulated in tumor tissue. The genes whose mRNA levels were significantly related to the five hub gene AS events were significantly enriched in the GO term of cell division and Notch signaling pathway. Further coexpression of gene AS events and alternative splicing factor genes revealed NOVA1 as a crucial factor regulating the hub gene AS event expression in CRC. Through in vitro experiments, we found that NOVA1 inhibited gene AS event SORBS2, which induced the migration of CRC cells via the Notch pathway. Conclusion: Integrated analysis of gene expression and gene AS events and further experiments revealed that NOVA1-mediated SORBS2 promoted the migration of CRC, indicating its potential as a therapeutic target.

19.
Physiol Genomics ; 53(12): 518-533, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34714176

RESUMO

Integration of microbiota in a host begins at birth and progresses during adolescence, forming a multidirectional system of physiological interactions. Here, we present an instantaneous effect of natural, bacterial gut colonization on the acceleration of longitudinal and radial bone growth in germ-free born, 7-wk-old male rats. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. In addition, the number of small in size adipocytes increased, whereas the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats indicating that not only bone mass but also bone marrow environment is under control of gut microbiota signaling. The changes in bone status paralleled with a positive shift in microbiota composition toward short-chain fatty acids (SCFA)-producing microbes and a considerable increase in cecal SCFA concentrations, specifically butyrate. Furthermore, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels. Elevated serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase. Overall, the presented model of conventionalized germ-free rats could be used to study microbiota-based therapeutics for combatting dysbiosis-related bone disorders.

20.
JCI Insight ; 6(20)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499623

RESUMO

Autophagy has long been associated with longevity, and it is well established that autophagy reverts and prevents vascular deterioration associated with aging and cardiovascular diseases. Currently, our understanding of how autophagy benefits the vasculature is centered on the premise that reduced autophagy leads to the accumulation of cellular debris, resulting in inflammation and oxidative stress, which are then reversed by reconstitution or upregulation of autophagic activity. Evolutionarily, autophagy also functions to mobilize endogenous nutrients in response to starvation. Therefore, we hypothesized that the biosynthesis of the most physiologically abundant ketone body, ß-hydroxybutyrate (ßHB), would be autophagy dependent and exert vasodilatory effects via its canonical receptor, Gpr109a. To the best of our knowledge, we have revealed for the first time that the biosynthesis of ßHB can be impaired by preventing autophagy. Subsequently, ßHB caused potent vasodilation via potassium channels but not Gpr109a. Finally, we observed that chronic consumption of a high-salt diet negatively regulates both ßHB biosynthesis and hepatic autophagy and that reconstitution of ßHB bioavailability prevents high-salt diet-induced endothelial dysfunction. In summary, this work offers an alternative mechanism to the antiinflammatory and antioxidative stress hypothesis of autophagy-dependent vasculoprotection. Furthermore, it reveals a direct mechanism by which ketogenic interventions (e.g., intermittent fasting) improve vascular health.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...